Modulatory effects of neurotoxic insecticides on the peripheral and central GABA-ergic action

On the terminal part of the guinea-pig ileum GABA produces
contraction, whereas on the preterminal it produces an initial shortlasting
contraction, followed by a prolonged relaxation. The increasing
range of concentrations of GABA produces a concentration-dependent
decrease in contractions and an increase in contractions of the
preterminal ileum. Both contractions and relaxations can be blocked by
atropine, indicating the cholinergic nature of the responses. These
effects are due to the action on GABAA receptors.
Depending on the duration of the incubation period (3 and 60
sec) GABA produced either potentiation or depression of the
contractile effects of acetylcholine on the ileum.
All the three neurotoxic insecticides (lindan, malathion,
permethrine) affect the contractile effects of acetylcholine on the ileum.
Lindan and permetrine antagonized the contractile effects of
acetylcholine, whereas malathion produced a potentiation. Malathion
significantly depressed the contractile effects of the electrical field
stimulation of the ileum. This effect is probably realized through the
local release of GABA.
Both lindan and permethrine were found to decrease the duration
of the barbiturate sleeping time, whereas malathion significantly
prolonged its duration. The action of lindan and permethrine is
presumably realized by blocking or interfering with the function of
GABAA receptors. Malathion is an anticholinesterase, thus producing
an accumulation of acetylcholine at the critical sites, consequently
producing a prolongation of the barbiturate sleeping time.
In conclusion, neurotoxic insecticides (lindan, permethrine,
malathion) affect both central and peripheral GABA-ergic systems.
They can produce either depression or stimulation of these systems.
They also highly significantly modulate the activity of the cholinergic
system in the isolated guinea-pig ileum.